RESUMO
BACKGROUND: Approximately 5% of adult cancer interventions put into clinical testing attain regulatory approval. Little is known about corresponding rates for pediatric cancer. METHODS: Our primary outcomes were the proportion of interventions graduating to the next trial phase, randomized trials, and/or clinical practice. We created a saturation sample of clinical trials by searching ClinicalTrials.gov for all pediatric anticancer trials in the United States or Canada. Trial characteristics were extracted automatically from ClinicalTrials.gov records, and cancer indication/drug class categorization, biomarker enrichment, and Food and Drug Administration (FDA) approval status at time of recruitment were double-extracted from each record. Regulatory approval status and labeling modifications for each intervention were determined by searching Drugs@FDA and the New Pediatric Labeling Information Database. RESULTS: Five hundred eighty-nine pediatric trials launched between 1987 and 2019 were captured. The overall probability of graduation was 17.0%; 18.9% of interventions graduated from phase 1 to phase 2 trials, and 1.6% of interventions graduated from phase 2 to phase 3 trials. The proportion of interventions advancing from phase 1 to FDA approval was 3.6%, and 1.9% of interventions tested in phase 1 advanced to a randomized phase 2 trial. Only biomarker enrichment was significantly predictive of graduation from phase 1 to phase 2 trials (p = .011). CONCLUSION: The proportion of interventions advancing from phase 1 testing to FDA approval was similar to estimates for adult oncology. Our findings highlight the challenges for current paradigms of pediatric anticancer drug development.